ID HYAL2_SHEEP Reviewed; 476 AA.
AC Q8SQG7;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 24-JAN-2024, entry version 104.
DE RecName: Full=Hyaluronidase-2;
DE Short=Hyal-2;
DE EC=3.2.1.35;
DE AltName: Full=Hyaluronoglucosaminidase-2;
DE Flags: Precursor;
GN Name=HYAL2;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11836391; DOI=10.1128/jvi.76.5.2141-2149.2002;
RA Dirks C., Duh F.-M., Rai S.K., Lerman M.I., Miller A.D.;
RT "Mechanism of cell entry and transformation by enzootic nasal tumor
RT virus.";
RL J. Virol. 76:2141-2149(2002).
RN [2]
RP INTERACTION WITH JSRV ENVELOPE PROTEINS.
RX PubMed=11296287; DOI=10.1073/pnas.071572898;
RA Rai S.K., Duh F.-M., Vigdorovich V., Danilkovitch-Miagkova A., Lerman M.I.,
RA Miller A.D.;
RT "Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-
RT anchored cell-surface receptor for jaagsiekte sheep retrovirus, the
RT envelope protein of which mediates oncogenic transformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:4443-4448(2001).
CC -!- FUNCTION: Hydrolyzes high molecular weight hyaluronic acid to produce
CC an intermediate-sized product which is further hydrolyzed by sperm
CC hyaluronidase to give small oligosaccharides. Displays very low levels
CC of activity. Associates with and negatively regulates MST1R (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-
CC glucosamine and D-glucuronate residues in hyaluronate.; EC=3.2.1.35;
CC -!- SUBUNIT: Interacts with MST1R (By similarity). Interacts with
CC Jaagsiekte sheep retrovirus (JSRV) envelope proteins. {ECO:0000250,
CC ECO:0000269|PubMed:11296287}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor, GPI-
CC anchor {ECO:0000250}.
CC -!- MISCELLANEOUS: Acts as a receptor for the Jaagsiekte sheep retrovirus
CC (JSRV), which induces ovine pulmonary adenocarcinoma. A possible
CC mechanism is that binding to JSRV envelope proteins may liberate the
CC oncogenic factor MST1R that is normally negatively regulated by HYAL2,
CC leading to oncogenic transformation.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 56 family. {ECO:0000305}.
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DR EMBL; AF411974; AAL78386.1; -; mRNA.
DR RefSeq; NP_001009754.1; NM_001009754.1.
DR RefSeq; XP_011954627.1; XM_012099237.2.
DR RefSeq; XP_011954628.1; XM_012099238.2.
DR RefSeq; XP_011954629.1; XM_012099239.2.
DR AlphaFoldDB; Q8SQG7; -.
DR SMR; Q8SQG7; -.
DR STRING; 9940.ENSOARP00000010309; -.
DR CAZy; GH56; Glycoside Hydrolase Family 56.
DR GlyCosmos; Q8SQG7; 4 sites, No reported glycans.
DR PaxDb; 9940-ENSOARP00000010309; -.
DR Ensembl; ENSOART00000010462.1; ENSOARP00000010309.1; ENSOARG00000009614.1.
DR Ensembl; ENSOART00020021134; ENSOARP00020017491; ENSOARG00020013831.
DR GeneID; 443154; -.
DR KEGG; oas:443154; -.
DR CTD; 8692; -.
DR eggNOG; ENOG502QUYI; Eukaryota.
DR HOGENOM; CLU_036366_0_0_1; -.
DR OMA; TKNRESC; -.
DR OrthoDB; 5344684at2759; -.
DR Proteomes; UP000002356; Chromosome 19.
DR Bgee; ENSOARG00000009614; Expressed in prescapular lymph node and 52 other cell types or tissues.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IEA:Ensembl.
DR GO; GO:0005540; F:hyaluronic acid binding; ISS:UniProtKB.
DR GO; GO:0033906; F:hyaluronoglucuronidase activity; ISS:UniProtKB.
DR GO; GO:0004415; F:hyalurononglucosaminidase activity; ISS:UniProtKB.
DR GO; GO:0030294; F:receptor signaling protein tyrosine kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0050431; F:transforming growth factor beta binding; IEA:Ensembl.
DR GO; GO:0001618; F:virus receptor activity; ISS:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0051216; P:cartilage development; ISS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0071493; P:cellular response to UV-B; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:Ensembl.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; ISS:UniProtKB.
DR GO; GO:0006027; P:glycosaminoglycan catabolic process; ISS:UniProtKB.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0030214; P:hyaluronan catabolic process; ISS:UniProtKB.
DR GO; GO:0042117; P:monocyte activation; ISS:UniProtKB.
DR GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0035810; P:positive regulation of urine volume; ISS:UniProtKB.
DR GO; GO:0070295; P:renal water absorption; ISS:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0009615; P:response to virus; ISS:UniProtKB.
DR GO; GO:0048705; P:skeletal system morphogenesis; IEA:Ensembl.
DR GO; GO:0046718; P:viral entry into host cell; ISS:UniProtKB.
DR Gene3D; 3.20.20.70; Aldolase class I; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR018155; Hyaluronidase.
DR PANTHER; PTHR11769; HYALURONIDASE; 1.
DR PANTHER; PTHR11769:SF6; HYALURONIDASE-2; 1.
DR Pfam; PF01630; Glyco_hydro_56; 1.
DR PIRSF; PIRSF038193; Hyaluronidase; 1.
DR PRINTS; PR00846; GLHYDRLASE56.
DR SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; EGF-like domain; Glycoprotein; Glycosidase;
KW GPI-anchor; Host-virus interaction; Hydrolase; Lipoprotein; Membrane;
KW Receptor; Reference proteome; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..451
FT /note="Hyaluronidase-2"
FT /id="PRO_0000239065"
FT PROPEP 452..476
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000239066"
FT DOMAIN 364..442
FT /note="EGF-like"
FT ACT_SITE 138
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT LIPID 451
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000255"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 47..343
FT /evidence="ECO:0000250"
FT DISULFID 214..230
FT /evidence="ECO:0000250"
FT DISULFID 368..379
FT /evidence="ECO:0000250"
FT DISULFID 373..430
FT /evidence="ECO:0000250"
FT DISULFID 432..441
FT /evidence="ECO:0000250"
SQ SEQUENCE 476 AA; 54229 MW; 427C9277ACF7AAAA CRC64;
MWTGLGPAVT LALVLVVAWA TELKPTAPPI FTGRPFVVAW DVPTQDCGPR HKMPLDPKDM
KAFDVQASPN EGFVNQNITI FYRDRLGMYP HFNSVGRSVH GGVPQNGSLW VHLEMLKGHV
EHYIRTQEPA GLAVIDWEDW RPVWVRNWQD KDVYRRLSRQ LVASHHPDWP PERIVKEAQY
EFEFAARQFM LETLRFVKAF RPRHLWGFYL FPDCYNHDYV QNWETYTGRC PDVEVSRNDQ
LSWLWAESTA LFPSVYLEET LASSTHGRNF VSFRVQEALR VADVHHANHA LPVYVFTRPT
YSRGLTGLSE MDLISTIGES AALGAAGVIL WGDAGFTTSN ETCRRLKDYL TRSLVPYVVN
VSWAAQYCSW AQCHGHGRCV RRDPNAHTFL HLSASSFRLV PSHAPDEPRL RPEGELSWAD
RNHLQTHFRC QCYLGWGGEQ CQWDRRRAAG GASGAWAGSH LTGLLAVAVL AFTWTS
//
